We propose to investigate the reflex functions and afferent characteristics of pulmonary nerve endings, particularly those responsive to stimuli delivered via the pulmonary vasculature. Our studies will concentrate on those stimuli that are likely candidates for mediating the phenomenon of exercise hyperpnea, the sensation of dyspnea and the reflex bronchial constriction of cardiac asthma. We will more completely characterize the cardiovascular and pulmonary reflexes elicited by changes in pulmonary arterial PO2, PCO2 and temperature as well as changes in pulmonary blood flow and pulmonary vascular pressures. To accomplish these studies, we have devised a unique preparation which allows us to control the blood flow, venous pressures and blood gases in the pulmonary circulation independent of those in the systemic circulation. Systemic venous return will be removed from the right atrium of anesthetized dogs and will then be pumped through a membrane gas exchanger, heat exchanger and returned to the aorta. An identical bypass will be established for the pulmonary circulation, removing blood from the left atrium and returning it to the pulmonary artery. With this preparation, we will assess changes in respiratory drive, airway smooth muscle tone, systemic vascular resistance, the distribution of cardiac output and venous compliance produced by the stimuli under study. Airway tone will be assessed by measuring the isometric tension in an isolated tracheal segment. Respiratory drive will be assessed by measuring phrenic nerve activity. We will also investigate the response of vagal afferent nerve endings to various pulmonary stimuli. We shall record impulses from "single fibers" supplying the various different types of pulmonary afferents, examining their response to graded stimuli. In particular, we shall attempt to construct for pulmonary afferents, CO2- and O2-response curves comparable to those that have been described for arterial chemoreceptor fibers.